βSubunits Promote K + Channel Surface Expression through Effects Early in Biosynthesis

• Published in: Neuron (Cambridge, Mass.) Mass.), 1996-04, Vol.16 (4), p.843-852
• Main Authors: Shi, Gongyi, Nakahira, Kensuke, Hammond, Scott, Rhodes, Kenneth J, Schechter, Lee E, Trimmer, James S
• Format: Article
• Language: English
• Subjects: Animals; Brain Chemistry; Cattle; Cell Line; Cell Membrane - metabolism; Elapid Venoms - metabolism; Electrophoresis, Polyacrylamide Gel; Fluorescent Antibody Technique, Indirect; Gene Expression; Glycosylation; Immunohistochemistry; Immunosorbent Techniques; Macromolecular Substances; Mice; Potassium Channels - biosynthesis; Potassium Channels - chemistry; Potassium Channels - genetics; Protein Biosynthesis; Rats; Transfection
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(00)80104-X

Voltage-gated K + channels are protein complexes composed of ion-conducting integral membrane α subunits and cytoplasmic β subunits. Here, we show that, in transfected mammalian cells, the predominant β subunit isoform in brain, Kvβ2, associates with the Kv1.2 α subunit early in channel biosynthesis and that Kvβ2 exerts multiple chaperone-like effects on associated Kv1.2 including promotion of cotranslational N-linked glycosylation of the nascent Kv1.2 polypeptide, increased stability of Kvβ2/Kv1.2 complexes, and increased efficiency of cell surface expression of Kv1.2. Taken together, these results indicate that while some cytoplasmic K + channel β subunits affect the inactivation kinetics of α subunits, a more general, and perhaps more fundamental, role is to mediate the biosynthetic maturation and surface expression of voltage-gated K + channel complexes. These findings provide a molecular basis for recent genetic studies indicating that β subunits are key determinants of neuronal excitability.